Preparation of dialkyl glycolurils



Patented Oct. 6, 1953 UNITED STATES PATENT OFFICE 2,654,763 PREPARATION OF DIALKYL GLYCOLURILS Homer B. Adkins, Madison, of America United States Secretary of the Navy No Drawing. Application April 17, 1943, Serial No. 483,499

3 Claims. (01. 260-30937) l The present invention is concerned with the production of 1,2-diketones and certain uril and halouril derivatives thereof.

It is well known that the nitrosation of ketones of the type R-CO-CH2R with ethyl nitrite produces 1,2-diketone monoximes,

which may be hydrolyzed in dilute acid to the corresponding diketone, RCO-CO-R. It is also known that 1,2-diketones readily condense with urea to produce glycolurils (I) which may be converted to the tetrachloroglycolurils (II) by chlorination with hypochlorous acid.

Among the known processes of producing glycoluril from the reaction of monoxime with urea is the process for preparing dimethyl glycoluril by adding concentrated sulfuric acid to a Chemie, vol. XXVI, page 445.

The present invention is related to the foregoing series of reactions and is based on the discovery that glycolurils (I) may be obtained directly from the reaction mixture resulting from nitrosation of ketones of type RCO--CH2R. Thus, in accordance with the urea under uril-forming conditions, the process oii'ering the distinct advantage that no intermediate preparative or purification steps are necessary.

By the process of the g with may be produced from 100 grams of methyl ethyl ketone.

In order more clearly to disclose the nature of Wis., assignor to the as represented by the tion upon the spirit and scope of the invention as defined in the appended claims.

EXAMPLE I (Nitrosation with ethyl nitrite) In a 300 ml., round-bottomed, three-necked flask equipped with a reflux condenser, a therby passing in lows pear in the nitrosation flask, and the temperature fell below 40 C. nected. The volume of the nitrosation Was usually 206-210 ml. not allowed to exceed 55 otherwise it was red.

solution If the temperature was C., the color was yellow;

The dimethylglycoluril may be chlorinatedas 1 mole (1'70 g.) of dimethylglycoluril follows: (either crude or purified); 4.5 mo1es(380 g;) of sodium bicarbonate; 2 liters of tap water and 5 ml. of aqueous wetting agent (e. g-.,-the-dioctyl ester of sodium sulfosuccinate sold'u'n'derH the trade name of Aerosol OT) was placed in a three-liter round-bottomed flask fitted with a stirrer. The mixture was heated to 40 C. and chlorine gas was passed through a gas feed stirrer and intothemixture at the rate of -80 g. of chlorine per hour. The temperature of themixture graduall roseto-about 46-4? C. in 4 hours and chlorine became visible in the atmosphere above the liquidrin the flask at the end-of this period. Afiaerd hours, the chlorine feed was reduced to 30rg.-perhour after which the fiow of chlorine wasmontinueduntil150g; of chlorine had been added: Themixture was then filtered and the 1 solidwaswashed-with 1' liter of'tap water. The" product-was dried in the air for to hours. The-dried material weighed approximately 280 to 290 :g. and consisted of relatively pure tetrachlorodimethylglycolur-il.

EXAMPLE II (Nitro'satz'on with nitrous acid) Iriraone liter, three-necked, round-bottomed flask; equippe'dwith'a reflux. condenser, a mechanical stirrer, and a dropping funnel, the

stem 'o f which extended well down into the fiask, was placed 125ml. (100 g., 1.38 moles) ofmethylQ ethyl'ketone; 300 ml. of water, and 105 ml. of

concentrated hydrochloric acid (spl gr. 1.18-1.20).

The mixture was held at a temperature of 50-55% (3., while-to itwasslowly added a solutionof 85 g. (1203 moles) of sodium nitrite in 100 ml.

of water. Thisoperation required from forty to eighty minutes with intermittent cooling. Early thenitrosation', the mixture took. on a yellowgreen' color'. If the rate of addition 'of the sodium nitrite'w"as-*too rapid, the color became yellow orbrown-, and nitrogen dioxide was evolved from.

the-condenser. As the nitrosation proceeded the color of the reaction mixture usually became more yellow-and" at its completion there was a slight evolutionpfnitrogen dioxide. The normal yellow-green color returned when the nitrogen dioxide was no longer evolved.

Af-ter the addition of the sodium nitrite solutiori wa's"completed, another ml. ofco'ncene trated hydrochlorioracid'was added, and stirring was =coiitinued until the temperature fell below 50 C), which required fifteenitothirty minutes.

Eighty-five g. (1.4 moles) offurea'was dissolved iii-this mixture, and the solution was allowed to stand at room temperature. Dimeth-yl glycoluril formedve'ry rapidly at first, but'the ratedecreased 'so'thata fifteen to twenty-hour period" was necessary-for complete precipitation. Du'r ing:'this time* the mixtureshould not be stored in-tightly stoppered containers; since it isusually slightly; efiervescent. Its color changed rather alcohol or with a solution of g."

' should be mentioned that rapidly to a deep red early in the condensation period. After the condensation period, the dimethylglycoluril was filtered off, washed by suspension in 1 liter of water at 60, cooled to room temperature, filtered with suction, and dried. The final product was usually pink in color. A yield of" about 65-'g.-,-or- 28- 31% of the theorectical, was obtained.

In connection with the foregoing example, it the manner in which the nitrosation step is. carried out exerts an important influence on the yield. In general, it has been found thatasignificant improvement in yield: is attainedin the nitrosation of watersoluble Tketones of the type nique which offersdistinct advantages. 7

As previously stated, the proceduredescribem abovefor the conversion of methyl ethylketone to the-corresponding glycoluril may. beapplied" generally to ketones of the type:

Thus for example, the process may be applied to methyl 'isobutyl-ketone. In short, bythe process of the present invention, ketones of the class described may be converted to the corresponding uril without the necessity of isolation and hy drolyzi'ng.- the 'diketone 'monox-ime resulting from the' 'nitro's'ation reaction; 1

Althoughthe "process of the 1 present invention-- is; of course','.ir'1 no .-manner dependent upon any mechanism; whichmay be postulated to explain the formation of glycolurils conditions; neverthelessa. brief dis'cu'ssion 'ofJthepossible reactions involved .may' 'beo'f assistance? in; understanding: the reasonsfor the different purification techniques -'used in- Examples I and? II: With this purpose in yiew,xtheifollowing com ments areofieredz.

It appe-ars that, in the formation of glycolurils in accordancenwiththe presentinvention; a nu'mher of competitive reactions-tmkeplace. Thus; .iI'i-Jv the case of methyl ethyl 'ketone', someofthepos; sible reactions involved maybe represented as: follows:-

(2-) Disproportiondtion CH3C=O' under the stated (4) Uril formation While all of the foregoing postulated reactions and equilibria (as well as others) may take place under all conditions, it appears that the nature of the nitrosation medium exerts an important influence on the rate and extent of the second and third reactions suggested above. Considering, firstly, the case where the uril is formed from the nitrosation reaction mixture obtained by the use of the aqueous nitrous acid, the course of the possible reactions depends on whether or not an excess of methyl ethyl ketone has been used in the nitrosation step. If none of the starting ketone is present during uril formation, reactions 1, 2 and 4 appear to predominate. At any rate, under these conditions, dimethylglyoximeis formed in addition to the glycoluril. If, however, an excess of methyl ethyl ketone is present in the nitrosation reaction mixture, reactions 1, 3 and 4 appear to predominate, the oxime acceptance reaction (3) apparently taking place at the expense of the disproportionation reaction (2). In this latter case (regardless of the mechanism), the reaction product contains little if any glyoxime, the oxime of methyl ethyl ketone being one of the principal by-products obtained under such conditions. Since the latter oxime is water soluble and therefore more easily removed, the presence of excess methyl ethyl ketone during uril formation offers certain advantages.

Considering now the case where uril formation occurs in the nitrosation reaction mixture obtained by the use or an alcoholic alkyl nitrite, reactions 1, 2 and 4 appear to predominate under all conditions: i. e., glyoxime and glycoluril are produced although some oxime oi. the starting ketone may also be formed. Thus it will be seen that the method or nitrosation determines the character of the principal non-gaseous by-products produced during uril formation. Accordingly, certain modifications in the purification techniques employed to separate the uril from the non-gaseous by-products may be required, depending on the conditions of nitrosation, even though the yield of uril in Examples I and II is substantially the same in both cases.

It will be apparent from considerations of yield of glycoluril that other reactions take place in addition to those herein suggested. It therefore should be clearly understood that the process or the invention, while perhaps more readily understandable in the light of the foregoing tentatively suggested explanation, is in no way dependent upon the correctness thereof.

It will also be apparent that many obvious variations may be made in the details given in the foregoing illustrative examples, and the invention should not be limited other than as defined by the appended claims.

I claim:

1. A method for preparing a dialkyl glycoluril which comprises nitrosating a 1.2-dia1kyl ketone to the ketone oxime by adding an alkali metal nitrite to the ketone in solution in dilute aqueous strong mineral acid, the ketone being in excess, adding urea to the aqueous nitrosation reaction mixture in the presence of dilute strong mineral acid and eifecting therein, hydrolysis of the ketone oxime to the diketone and condensation of the latter with the urea to the dialkyl glycoluril.

2. A method of preparing dimethyl glycoluril which comprises subjecting methyl ethyl ketone in solution in dilute aqueous strong mineral acid to nitrosation with nitrous acid to form the ketone oxime, the ketone being in excess, adding urea to the aqueous nitrosation reaction mixture in the presence of dilute strong mineral acid and the excess ketone and effecting therein, hydrolysis of the ketone oxime to dimethyl diketone and condensation of the latter with the urea to dimethyl glycoluril.

3. A method of preparing dimethyl glycoluril which comprises nitrosating methyl ethyl ketone to the ketone oxime by adding an alkali metal nitrite to the ketone in solution in dilute aqueous strong mineral acid, the ketone being in excess, adding urea to the aqueous nitrosation reaction mixture in the presence of dilute strong mineral acid and the excess ketone and eifecting therein, hydrolysis of the ketone oxime to dimethyl diketone and condensation of the latter with the urea to dimethyl glycoluril.

HOMER B. ADKINS.

References Cited in the file of this patent 

1. A METHOD FOR PREPARING A DIALKYL GLYCOLURIL WHICH COMPRISES NITROSATING A 1,2-DIALKYL KETONE TO THE KETONE OXIME BY ADDING AN ALKALI METAL NITRILTE TO THE KETONE IN SOLUTION IN DILUTE AQUEOUS STRONG MINERAL ACID, THE KETONE BEING IN EXCESS, ADDING UREA TO THE AQUEOUS NITROSATION REACTION MIXTURE IN THE PRESENCE OF DILUTE STRONG MINERAL ACID AND EFFECTING THEREIN, HYDROLYSIS OF THE KETONE OXAMINE TO THE DIKETONE AND CONDENSATION OF THE LATTER WITH THE UREA TO THE DIALKYL GLYCOLURIL. 